OBJECTIVE Basal plasma T4, T3 and TSH concentrations are usually normal in patients presenting with non-toxic nodular goitre. Using the evaluation of TSH response to TRH in a large series of such patients living in an area with normal iodine intake, we evaluated the prevalence of subclinical hyperthyroidism and the relationship between thyroid hormonal status and ultrasonographic parameters. METHODS A prospective study of 242 consecutive patients (group I), referred with non-autoimmune nodular goitre, normal plasma free T4, total T3 and TSH levels, without (subgroup IA, 222 patients) or with (subgroup IB, 20 patients) clear-cut autonomous area(s) on scintigraphy. These patients were compared to 135 controls (group II). METHODS Plasma free T4 (FT4), total T3 (T3T) and TSH measurements. Evaluation of TSH response to TRH (delta level of increased TSH = peak TSH level during TRH test-basal TSH level), thyroid scintigraphy and morphological characteristics (number and total volume of nodule(s) and volume of extranodular tissue) determined by ultrasonography. RESULTS In subgroup IA, (1) the mean (+/- SEM) basal TSH level (0.94 +/- 0.04 mU/I) and the mean value of increased TSH after TRH (4.92 +/- 0.34 mU/I) were lower (P < 0.001) than in group II (1.28 +/- 0.05 mU/I and 7.24 +/- 0.25 mU/I, respectively). The prevalence of SH (delta level of increased TSH below the mean -3 SD in controls) was 17.2%; (2) the mean FT4 level and the mean T3T value were not different (P > 0.05) from those of group II. In subgroup IB, (1) the mean basal TSH level (0.57 +/- 0.11 mU/I) and the mean increment of TSH after TRH (2.81 +/- 0.62 mU/I) were lower (P < 0.001) than in subgroup IA. The prevalence of subclinical hyperthyroidism was 75.0%; (2) the mean FT4 level (17.2 +/- 0.9 pmol/I) was not different from that in group II. However, the mean T3T value (1.99 +/- 0.01 nmol/I) was higher (P < 0.001) than in group II (1.65 +/- 0.05). In group I, subgroup IA and IB, there were significant (P < 0.05, at least) correlations between the numbers of nodules and both basal TSH levels and delta values of increased TSH or FT4 levels or T3T values. No correlations were found between other ultrasonographic data and plasma thyroid parameters. CONCLUSIONS This study demonstrates a high prevalence of subclinical hyperthyroidism in patients presenting with non-toxic nodular goitres and suggests that the number of nodules, but not their total volume, is an important factor in the development of this condition.